JP7126163B2 - Methods for Assessing Lymphatic System Function - Google Patents

Description

Embodiments relate to methods of assessing lymphatic system function.

The lymphatic system is a network of lymph nodes, lymphatic vessels and other lymphoid tissues that act as a circulatory system for lymphatic fluid. Methods for diagnosing lymphatic system diseases (e.g., lymphedema) include injecting fluorescent dyes such as indocyanine green and imaging lymphatic vessels by fluorescence observation, etc., and injecting radioactive isotopes such as ^99m Tc-labeled tin colloids. However, lymphatic imaging methods such as scintigraphic visualization methods are known (e.g., Non-Patent Document 1 and Non-Patent Document 2)

Unno N. et al., J. et al. Vasc. Surg. , 2007, Vol. 45, No. 5, pp. 1016-1021 MaegawaJ. et al., Microsurgery, 2010, Vol. 30, No. 6, pp. 437-442

Lymphatic angiography is an essential examination for diagnosing lymphedema, but it has fundamental problems stemming from anatomical problems. Since there are countless lymphatic vessels starting from blind ends, there are countless candidates for injection sites of the contrast medium. In addition, there have been no reports that examined the relationship between the origin of the lymphatic system and the associated lymphatic vessels and lymph nodes. In other words, there is no information that can grasp the relationship between the injection site of the contrast medium and the corresponding lymphatic route into which the contrast medium is taken and imaged. Therefore, there is no conventionally performed lymphography examination that can determine the injection site with anatomical evidence. This has led to the development of different injection site testing protocols.

In fact, in the case of the lower extremities, contrast agents are often injected only into the first interdigital region, targeting the anteromedial bundle that accompanies the great saphenous vein. Sometimes there are. It has not been investigated whether the test results can be similarly compared even though the injection sites are different. Furthermore, in some cases, a contrast agent is injected near the heel, targeting the posterolateral bundle that accompanies the lesser saphenous vein, but there is no information on the origin corresponding to it, and the posterolateral bundle can be imaged reliably. The designated injection site is unknown. Similarly, there is no established information for the upper extremities.

The lack of a unified and complete examination protocol for imaging the lymphatic system means that there is no common basis for judging treatment strategies and their effects, not only at the time of diagnosis.

The inventors have successfully mapped the anatomical information required for injection site determination during lymphography studies of the lower and upper extremities, and the details of the lymphatic routes that can be imaged thereby. Based on this information, we clarified the relationship between the appropriate injection site for lymphography and the lymphatic route that can be visualized. The embodiments are based on these new findings, and aim to provide a lymphatic system function evaluation method using a lymphatic route map, and to provide a lymphatic system function evaluation device used in the evaluation method.

An embodiment is a method for evaluating the function of the lymphatic system, comprising a step of selecting one or more lymphatic routes to be evaluated from a plurality of lymphatic routes present in an extremity; Determining the injection site of the visualization agent based on information on the injection site of the extremities, injecting the visualization agent from the selected injection site, visualizing the injected visualization agent, and evaluating one or more and assessing the function of the lymphatic route of .

The embodiment comprises a first acquisition means for acquiring information on the injection site of the visualization agent in the extremities of the subject, a second acquisition means for acquiring a visualization agent image of the subject injected with the visualization agent, and a first Based on the information obtained by the obtaining means and the information on the plurality of lymphatic routes existing in the extremities and the corresponding injection sites in the periphery of the extremities, the visualization agent image obtained by the second acquiring means includes a plurality of lymphatic routes present in the extremities. The present invention also relates to a lymphatic system function evaluation apparatus comprising a color setting means for setting a different color for each lymphatic system, and an output means for outputting a visualization agent image colored by the color setting means.

In the embodiment, the computer comprises a first acquisition means for acquiring information on the injection site of the visualization agent in the extremities of the subject, a second acquisition means for acquiring a visualization agent image of the subject injected with the visualization agent, and a first Based on the information acquired by the acquiring means and the information on the lymphatic routes present in the extremities and the corresponding injection sites in the periphery of the extremities, the visualization agent image acquired by the second acquiring means includes a plurality of lymph nodes present in the extremities. It also relates to a lymphatic system function evaluation program for functioning as color setting means for setting different colors for each route and output means for outputting a visualization agent image colored by the color setting means.

Embodiments also relate to a computer-readable recording medium having a lymphatic system function evaluation program recorded thereon.

ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to provide the evaluation method of the lymph system function using a lymph route map.

FIG. 1 is a schematic diagram of a lower extremity showing injection sites 1 to 19 of a contrast medium. Each lower extremity injection site was set according to anatomical landmarks on the dorsum-plantar boundary, and the details are as follows. Leg injection site 1: Below the medial malleolus Leg injection site 5: Head of first metatarsal bone Leg injection site 6: Base of first proximal phalanx Leg injection site 7: 1st interdigit lower limb injection site 8: 2nd interdigit lower extremity injection site 9: 3rd interdigit lower extremity injection site 10: 4th interdigit lower extremity injection site 11: bottom of 5th proximal phalanx ( base of fifth proximal phalanx) Leg injection site 12: head of fifth metatarsal bone Leg injection site 16: Below the lateral malleolus Leg injection site 18: calcaneal tuberosity Leg injection site 3 Lower limb injection site 2: Midpoint between lower limb injection site 1 and lower limb injection site 5 Lower limb injection site 4: Midpoint between lower limb injection site 3 and lower limb injection site 5 Lower limb injection site 14: midpoint between leg injection site 12 and leg injection site 16 leg injection site 13: midpoint between leg injection site 12 and leg injection site 14 leg injection site 15: midpoint between leg injection site 14 and leg injection site 16 leg injection Site 17: midpoint between leg injection site 16 and leg injection site 18 Leg injection site 19: midpoint between leg injection site 18 and leg injection site 1 FIG. 2 is a schematic diagram of an upper extremity showing upper extremity injection sites 1 to 17 of a contrast agent. Each upper extremity injection site was set according to anatomical landmarks on the dorsum-palm boundary, and the details are as follows. Upper limb injection site 1: distal of radial styloid process Upper limb injection site 5: the first head of metacarpi Upper limb injection site 3: upper limb injection site 1 and upper limb injection site 5 Upper limb injection site 2: midpoint between upper limb injection site 1 and upper limb injection site 3 Upper limb injection site 4: midpoint between upper limb injection site 3 and upper limb injection site 5 Upper limb injection site 6: between the first interdigital Upper limb injection site 7: the second interdigital space Upper limb injection site 8: the third interdigital space Upper limb injection site 9: the fourth interdigital space Upper limb injection site 10: the fifth head of metacarpi upper extremity injection site 14: distal of radial styloid process upper extremity injection site 12: midpoint between upper extremity injection site 10 and upper extremity injection site 14 Upper limb injection site 11: Midpoint between upper limb injection site 10 and upper limb injection site 12 Upper limb injection site 13: Midpoint between upper limb injection site 12 and upper limb injection site 14 Upper limb injection site 16: Midpoint between upper limb injection site 1 and upper limb injection site 14 Point (volar side) Upper limb injection site 15: Midpoint between upper limb injection site 14 and upper limb injection site 16 Upper limb injection site 17: Midpoint between upper limb injection site 16 and upper limb injection site 1 FIG. 3 is a block diagram showing a schematic configuration of a lymphatic system function evaluation system according to one embodiment. FIG. 4 is a schematic diagram showing the hardware configuration of the lymphatic system function evaluation device according to one embodiment. FIG. 5 is a schematic diagram showing the functional configuration of the lymphatic system function evaluation device according to one embodiment. FIG. 6(A) is a photograph showing an example of the results of a lower extremity lymphography examination. "X" indicates the trailing edge of the lateral malleolus. "△" indicates the leading edge of the medial malleolus. “O” indicates calcaneal tuberosity. "□" indicates the anterior midpoint between the anterior edge of the medial malleolus and the posterior edge of the lateral malleolus. The heel side is "rear" and the opposite side is "front" with "x" and "triangle" as boundaries. “Inner” and “outer” are the calcaneal tuberosity (indicated by “○”) and the anterior midpoint between the anterior edge of the medial malleolus and the posterior edge of the lateral malleolus (indicated by “□”). was defined as the standard. With "○" and "□" as boundaries, the medial malleolus side is "inner" and the lateral malleolus side is "outer". FIG. 6(B) is a trace diagram obtained by tracing FIG. 6(A). FIG. 7A is a photograph showing an example of the result of angiography of the anteromedial root of the leg. "□" indicates the anterior midpoint between the anterior edge of the medial malleolus and the posterior edge of the lateral malleolus. “◇” indicates the midpoint between “□” and the tibial tuberosity. FIG. 7(B) is a trace diagram obtained by tracing FIG. 7(A). FIG. 8(A) is a photograph showing an example of the result of angiography of the anterolateral root of the leg. "X" indicates the trailing edge of the lateral malleolus. "□" indicates the anterior midpoint between the anterior edge of the medial malleolus and the posterior edge of the lateral malleolus. “◇” indicates the midpoint between “□” and the tibial tuberosity. FIG. 8(B) is a trace diagram obtained by tracing FIG. 8(A). FIG. 9A is a photograph showing an example of the result of angiography of the posteromedial root of the leg. "△" indicates the leading edge of the medial malleolus. FIG. 9(B) is a trace diagram obtained by tracing FIG. 9(A). FIG. 10 is a photograph taken by dissection after injecting a dye into the lymphatic vessel of the lower leg. FIG. 11 is a photograph taken by dissection after injecting a dye into the lymphatic vessel of the lower leg. FIG. 12 is a photograph taken by dissection after injecting a dye into the lymphatic vessel of the lower leg. FIG. 13 is a photograph taken by dissection after injecting a dye into the lymphatic vessel of the lower leg. FIG. 14 is a diagram schematically summarizing the results of FIGS. 10 to 13. FIG. FIG. 15 is a table mapping the relationship between the lower extremity injection sites 1 to 19 in each cadaver and the corresponding lymphatic route of the lower extremity (anteromedial route, posterolateral route, anterolateral route or posteromedial route). FIG. 16 is a graph showing the frequency at which imaging was possible for each lymphatic route of the leg (anteromedial route, posterolateral route, anterolateral route, or posteromedial route) for each leg injection site. FIG. 17 is a schematic diagram mapping the area occupied by each lymphatic route (anteromedial route, posterolateral route, anterolateral route, or posteromedial route) of the lower leg. FIG. 18(A) is a photograph showing a patient's lower extremity on which lymphatic angiography was performed by the method of the embodiment. FIG. 18(B) is a trace diagram obtained by tracing FIG. 18(A). FIG. 19 is a diagram showing the definition of the inguinal superficial lymph node group in the present specification. FIG. 20 is an image obtained by three-dimensionally constructing CT lymphangiography images showing the running of the lymphatic route when imaging the posteromedial route. FIG. 21 is a graph plotting the frequency of lymph nodes reached first by the posteromedial route. FIG. 22 is a three-dimensionally constructed CT lymphangiography image showing the running of the lymphatic route when the anteromedial route is imaged. FIG. 23 is a graph plotting the frequency of lymph nodes reached first by the anteromedial route. FIG. 24 is a three-dimensionally constructed image of CT lymphangiography showing the running of the lymphatic route when the anterolateral route is imaged. FIG. 25 is a graph plotting the frequency of lymph nodes reached first by the anterolateral route. FIG. 26 is an image obtained by three-dimensionally constructing CT lymphangiography images showing the running of the lymphatic route when imaging the posterolateral route. FIG. 27 is a graph plotting the frequency of lymph nodes reached first by the posterolateral route. FIG. 28 is a graph plotting the frequency of the second and subsequent lymph nodes reached by each lymphatic route of the lower extremities (lymph nodes reached by each lymphatic route other than the lymph nodes first reached). FIG. 29(A) is a photograph showing an example of the upper extremity lymphangiography test result. FIG. 29(B) is a trace diagram of FIG. 29(A). FIG. 30 is a diagram showing the definition of the upper limb region for explaining the running of the lymphatic route. FIG. 31 maps the relationship between upper extremity injection sites 1 to 17 in each donated body and the corresponding lymphatic routes of the upper extremity (subradial root, verniular root, radial root, ulnar root, and median forearm root). It is a table. Figure 32 shows the frequency at which imaging was possible for each lymphatic route (subradial route, vernier lumbar route, radial route, ulnar route, and median forearm route) (number of donors with which imaging was possible/total number of ) for each upper extremity injection site. FIG. 33 is a schematic diagram mapping the area occupied by each lymphatic route (the subradial root, the vernilar root, the radial root, the ulnar root, and the median forearm root) in the upper extremity.

Hereinafter, embodiments will be described in detail. However, the embodiments are not limited to these, and various modifications can be made along the gist of the embodiments.

[Method for evaluating the function of the lymphatic system]
The method of evaluating the function of the lymphatic system of the present embodiment includes the steps of selecting one or more lymphatic routes to be evaluated from a plurality of lymphatic routes present in the extremities; determining the injection site of the visualization agent based on information on the injection site; injecting the visualization agent from the selected injection site; visualizing the injected visualization agent; and Evaluating the functionality of the route.

As used herein, the "lymphatic system" includes lymph nodes, lymph vessels and other lymphoid tissues (eg, thoracic duct, thymus, spleen, etc.).

The selection step is a step of selecting one or more lymphatic routes to be evaluated from a plurality of lymphatic routes present in the extremities.

Lymphatic vessels that make up the lymphatic system often form independent lymphatic routes (lymphatic pathways) that do not communicate with each other in the extremities (particularly below the extremities). The selection step selects one or more lymphatic routes to be evaluated. In the selection step, a plurality of lymphatic routes may be selected as evaluation targets so as to cover all independent lymphatic routes that do not communicate with each other.

The selecting step may select one or more lymphatic routes to be evaluated from an anteromedial route, an anterolateral route, a posteromedial route, and a posterolateral route of the leg.

The anteromedial root, anterolateral root, posteromedial root, and posterolateral root of the leg are named according to the area through which the lymphatic vessels pass at the ankle joint level when the leg is divided into four regions at the ankle joint level. It is the lymphatic route of the lower extremities. Here, with the posterior edge of the lateral malleolus and the anterior edge of the medial malleolus as boundaries, the heel side is "back" and the opposite side is "front". With the calcaneus tuberosity and the anterior midpoint between the anterior edge of the medial malleolus and the posterior edge of the lateral malleolus as the boundary, the medial side is "inner" and the lateral side is "outer". The anteromedial route refers to the lymphatic route of the lower extremity through which the lymphatic vessels pass through the "anterior" and "inner" regions at the level of the ankle joint of the lower extremity. Similarly, the anterolateral route refers to the lymphatic route of the lower extremity through which the lymphatic vessels pass through the "anterior" and "outer" regions at the level of the ankle joint of the lower extremity. The posteromedial route refers to the lymphatic route of the lower extremity through which the lymphatic vessels pass through the "posterior" and "inner" regions at the level of the ankle joint of the lower extremity. The posterolateral route refers to the lymphatic route of the lower extremity through which the lymphatic vessels pass through the "posterior" and "outer" area at the level of the ankle joint of the lower extremity.

The selecting step may also select one or more lymphatic routes to be evaluated from the forearm median route, radial route, subradial route, ulnar route or vernier route of the upper extremity.

The forearm median route, radial route, subradial route, ulnar route and vernier lumbar route of the upper extremity are lymphatic routes of the upper extremity named based on the classification of the cutaneous venous system of the upper extremity, which runs roughly in line with each lymphatic route. be.

In the selection step, all of the anteromedial route, the anterolateral route, the posteromedial route, and the posterolateral route of the leg may be selected as evaluation targets. As a result, the functions of lymphatic vessels in the lower extremities can be comprehensively evaluated. Similarly, in the selection step, all of the forearm median root, radial root, subradial root, ulnar root, and vernier root of the upper limb may be selected for evaluation. As a result, the functions of lymphatic vessels in the upper extremities can be comprehensively evaluated.

The determination step is a step of determining the injection site of the visualization agent based on the information of the selected lymphatic route and the corresponding injection site of the periphery of the extremity.

Conventionally, there was no information that could grasp the relationship between the injection site of the visualization agent and the corresponding lymphatic route into which the visualization agent was taken and imaged. In the embodiment, as specifically shown in the examples below, the correspondence between the injection site of the visualization agent set based on the anatomical information and the corresponding lymphatic route into which the visualization agent is taken and imaged. Relationship mapping was successful (eg, FIGS. 1, 15 and 16 and FIGS. 2, 31 and 32). Then, based on the information (e.g., correspondence relationships shown in FIGS. 15 and 16, and FIGS. 31 and 32) or information equivalent thereto (e.g., information acquired about further specimens, etc.), the selected lymphatic route A visible injection site can be determined.

In the determination step, only one injection site may be selected for the selected one lymphatic route and determined as the injection site of the visualization agent, or two or more injection sites may be selected and determined as the injection sites of the visualization agent. You may As shown in Examples below, for example, in the anteromedial route and the anterolateral route of the lower extremity, there are two lower extremity injection sites where the probability of uptake of the visualization agent (contrast medium) exhibits a peak (maximum value). . For example, one of these lower extremity injection sites may be selected as the injection site of the visualization agent, or both of these lower extremity injection sites may be selected as the injection site of the visualization agent. may be chosen for the injection site).

For example, when the lymphatic route of the lower extremities is selected in the selection step, the injection site of the visualization agent may be one or more injection sites selected from lower extremity injection sites 1 to 19 shown in FIG. There may be one or more injection sites selected from lower extremity injection sites 1, 7, 14 and 16 shown.

Further, for example, when all of the anteromedial route, the anterolateral route, the posteromedial route, and the posterolateral route of the leg are selected as evaluation targets in the selection step, the injection site of the visualization agent is the leg injection site 1 shown in FIG. , 7, 14 and 16. By setting all of the lower limb injection sites 1, 7, 14 and 16 as injection sites of the visualization agent, all four lymphatic routes of the lower limb can be comprehensively evaluated.

Further, for example, when the upper extremity lymphatic route is selected in the selection step, the injection site of the visualization agent may be one or more injection sites selected from the upper extremity injection sites 1 to 17 shown in FIG. 2 may be one or more injection sites selected from upper extremity injection sites 4, 7, 9, 14 and 16 shown in FIG.

Further, for example, when all the forearm median route, radial route, subradial route, ulnar route and vernier route of the upper limb are selected as evaluation targets in the selection step, the injection site of the visualization agent is shown in FIG. Upper extremity injection sites 4, 7, 9, 14 and 16 may be used. By setting all of the injection sites 4, 7, 9, 14 and 16 of the upper extremity as injection sites of the visualization agent, all five lymphatic routes of the upper extremity can be comprehensively evaluated.

The visualization agent is not particularly limited as long as administration to the human body is permissible. A suitable visualization agent may be selected according to the visualization method (detection method). As the visualization agent, for example, a contrast agent conventionally used in lymphography (eg, lipiodol, indocyanine green, ^99m Tc-labeled tin colloid, etc.) can be used. In addition to conventional contrast agents, the visualization agents include, for example, other dyes (e.g., patent blue), fluorescent dyes (e.g., indicocarmine), radioisotope-labeled compounds (e.g., ^99m Tc-labeled technetium human serum albumin ) can also be used.

The injecting step is injecting the visualization agent through the selected injection site.

The method of injecting the visualization agent is not particularly limited, and a method similar to the conventional method of injecting a contrast medium can be employed. For example, a method of injecting a visualization agent dissolved or suspended in an appropriate solvent such as physiological saline or a buffer into an injection site using a syringe can be employed.

The evaluation step is a step of visualizing the injected visualization agent and evaluating the function of one or more lymphatic routes to be evaluated.

The visualization method of the visualization agent may be selected according to the type of visualization agent used. For example, when a fluorescent dye (e.g., indocyanine green, lipiodol, patent blue, indicocarmine) is employed as a visualization agent, an infrared observation camera equipped with a light source (or filter) that can excite and detect fluorescence of the fluorescent dye The system allows visualization and data collection. Examples of the infrared observation camera system include PDE (manufactured by Hamamatsu Photonics), Hyper Eye Medical System (manufactured by Mizuho), LIGHT VISION (manufactured by Shimadzu Corporation), SPY System (manufactured by Novadaq Technologies), and the like. . Further, for example, when a radioisotope-labeled compound (e.g., ^99m Tc-labeled tin colloid, ^99m Tc-labeled phytate, ^99m Tc-labeled technetium human serum albumin) is employed as a visualization agent, visualization and data collection are performed by a radiation detector. It is possible. Examples of radiation detectors include gamma cameras, single photon emission tomography (SPECT) devices, positron emission tomography (PET) devices, and SPECT-CT devices.

If the lymphatic route is not visualized as a result of visualizing the injected visualization agent, the reason may be that the lymphatic vessels have disappeared or the lymph cannot move within the lymphatic vessels. can be determined to be impaired. In addition, as a result of visualizing the injected visualization agent, if a lymphatic route different from the assumed lymphatic route from the injection site is visualized, the assumed lymphatic route may be damaged in some way, and the visualized lymphatic route may be an alternative. It can be determined that the function of the lymphatic system (lymphatic vessel) is similarly impaired.

In addition, since lymphatic vessels are connected to other lymphoid tissues such as lymph nodes, according to the method of the embodiment, not only lymphatic vessels but also lymph nodes and other lymphoid tissues can be selectively visualized. can. Therefore, for example, if the lymph node is not visualized, the reason may be that the lymph node has disappeared or the connection between the lymph vessel and the lymph node is interrupted. can be determined to be impaired.

The method of the embodiment can be applied to, for example, diagnosis of diseases such as primary lymphedema, secondary lymphedema, venous edema, and disuse edema, confirmation of therapeutic effects, prognosis diagnosis, and the like. Embodiment methods can also be applied, for example, to reverse mapping for the prevention of lymphedema after lymphadenectomy.

[Lymphatic system function evaluation device]
In one embodiment, the lymphatic system function evaluation device is used as a lymphatic system function evaluation system in combination with an imaging device. Examples of imaging devices include fluorescence detectors and radiation detectors.

FIG. 3 is a block diagram showing a schematic configuration of the lymphatic system function evaluation system 1 according to one embodiment. A lymphatic system function evaluation system 1 shown in FIG.

(camera unit)
The light irradiation device 5 includes a light source 5a that outputs excitation light L1 for exciting _a fluorescent dye for fluorescence observation of an observation target P (for example, _a subject), and output of the excitation light L1 from the light source 5a. and a light source control unit 5b for controlling the light source control unit 5b. The light source 5a is a light emitting element such as an LED (light emitting diode), an LD (laser diode) and an SLD (super luminescent diode), and a lamp light source such as a halogen lamp and a xenon lamp. output light. For example, when the fluorescent dye is ICG, the peak of the absorption wavelength of the fluorescent dye is around 800 nm in the body, so the light source 5a used has an output light wavelength of 700 nm to 810 nm, for example. The light source control unit 5b includes _a light irradiation control circuit (for example, , processor). The wavelength of the light output from the light source 5a preferably does not include the wavelength of fluorescence, but when the wavelength of the light output from the light source 5a includes the wavelength of fluorescence, the light irradiation device 5 outputs An optical filter (not shown) may be provided to block light having the same wavelength as the fluorescence wavelength among the emitted light.

The light irradiation control unit sets light irradiation conditions for excitation light irradiation by the light irradiation device 5 . Then, the light irradiation control section controls the light source control section 5b so as to irradiate the excitation light under the set light irradiation conditions. The light irradiation control unit is a light irradiation control circuit (for example, a processor) that sets light irradiation conditions and controls the light source control unit 5b. The light irradiation controller may be built in the lymphatic system function evaluation device D.

The imaging device ₃ is a device that captures an image of the observation light L2 containing fluorescence from the observed object P under the control of an imaging control unit (not shown). _The imaging device ₃ includes an optical filter 3a that transmits light including the wavelength of fluorescence emitted by the fluorescent dye and blocks light with the wavelength of the excitation light L1, and receives the observation light L2 that has passed through the optical filter 3a. an image sensor 3b that outputs image data by photoelectrically converting light from the image sensor 3b; Consists of The imaging device control unit 3c is an imaging control circuit (for example, a processor) that controls the frame rate, exposure timing, exposure time, signal readout, etc. of the imaging device 3b under the control of the imaging control unit. The imaging element 3b is an area image sensor such as a CCD image sensor or a CMOS image sensor, and has a light receiving surface composed of a plurality of two-dimensionally arranged pixels (photoelectric conversion elements). The imaging element 3b can variably adjust the exposure time under the control of the imaging control section 3c.

The imaging control unit is an imaging control circuit (for example, a processor) that controls the operation of the imaging device 3 . Specifically, for example, the imaging control unit sets imaging conditions such as exposure time, exposure timing, and frame rate of the imaging element 3b, and controls the imaging element control unit 3c to perform imaging based on the set imaging conditions. to control. Examples of the imaging element 3b include a CCD image sensor, a global shutter CMOS image sensor, a rolling shutter CMOS image sensor, and the like. The exposure time may be adjusted by an electronic shutter of a CCD image sensor or a CMOS image sensor, or by providing a physical diaphragm or shutter between the observation object P and the imaging device 3b and opening and closing them. You may control and you may adjust those opening-and-closing amounts. The imaging control unit may be built in the lymphatic system function evaluation device D.

With the camera unit 7 configured as described above, the imaging element 3b receives ₍ images) the observation light L2 containing fluorescence from the observation target P, and outputs image data accordingly. The lymphatic system function evaluation apparatus D acquires this image data (the visualization agent image of the subject injected with the visualization agent) by the second acquiring means.

(Lymphatic system function evaluation device)
The configuration of the lymphatic system function evaluation device D will be described. FIG. 4 is a schematic diagram showing the hardware configuration of the lymphatic system function evaluation device D according to one embodiment, and FIG. 5 is a schematic diagram showing the functional configuration of the lymphatic system function evaluation device D according to one embodiment. is.

As shown in FIG. 4, the lymphatic system function evaluation device D physically includes a main storage device such as a CPU D11, a ROM D12 and a RAM D13, an input device D14 such as a keyboard, a mouse and a touch screen, a display (touch screen ), a communication module D16 such as a network card for transmitting and receiving data with other devices such as the camera unit 7 (fluorescence detector), an auxiliary storage device D17 such as a hard disk, etc. Configured as a normal computer, including Each function of the lymphatic system function evaluation device D, which will be described later, is performed by loading predetermined computer software onto hardware such as the CPU D11, ROM D12, and RAM D13, thereby performing the input device D14 and output device under the control of the CPU D11 This is achieved by operating D15 and communication module D16 and reading and writing data in main storage devices D12 and D13 and auxiliary storage device D17.

As shown in FIG. 5, the lymphatic system function evaluation device D includes, as functional components, a first acquisition means D1, a second acquisition means D2, a color setting means D3, and an output means D4. In addition, the lymphatic system function evaluation apparatus D may further include, as functional components, an imaging controller that controls the imaging device and/or a light irradiation controller that controls the light irradiation device.

The first acquisition means D1 acquires information on the injection site of the visualization agent in the extremities of the subject. For example, by displaying a diagram as shown in FIG. Acquire information on the injection site of the visualization agent in the extremity periphery. Further, for example, when the output device is composed of a touch screen, by displaying a diagram as shown in FIG. 1 on the touch screen and touching the injection site where the visualization agent is injected, Information on the injection site of the visualization agent in the extremity periphery of the subject may be obtained.

The second acquiring means D2 acquires a visualization agent image (for example, a fluorescence image) of the subject injected with the visualization agent. For example, the second acquisition means acquires a visualization agent image (for example, a fluorescence image, a radiation image) output by the imaging device.

The color setting means D3 obtains the visualization agent image obtained by the second obtaining means based on the information obtained by the first obtaining means and the information on the plurality of lymphatic routes present in the extremities and the corresponding injection sites in the periphery of the extremities. In addition, a different color is set for each lymphatic route present in a plurality of extremities. For example, lymphatic routes in the lower extremities can be classified into at least four lymphatic routes (anteromedial route, anterolateral route, posteromedial route and posterolateral route), and the lymphatic route through which the visualization agent flows differs depending on the injection site of the visualization agent. Therefore, the color setting unit provides information on the injection site of the visualization agent, and information on the lymphatic route of the lower extremity and the corresponding injection site on the periphery of the lower extremity (for example, information on the correspondence shown in FIGS. 1, 15, and 16). , or corresponding information (e.g., information obtained about additional specimens)), the visualization agent image has a color corresponding to each lymphatic route (e.g., blue for the anteromedial route, green for the anterolateral route, green for the posterior The medial route is purple, the posterolateral route is red, etc.). This makes it easier to visually grasp each lymphatic route and facilitate evaluation of the lymphatic system. Further, for example, the lymphatic route in the upper extremities can be classified into at least five lymphatic routes (forearm median route, radial route, subradial route, ulnar route, and vernilar route). Different lymphatic routes. Therefore, the color setting unit provides information on the injection site of the visualization agent, information on the lymphatic route of the upper extremity and the corresponding injection site of the upper extremity (for example, information on the correspondence shown in FIGS. 2, 31 and 32, Or based on the corresponding information (e.g., information obtained for additional specimens, etc.)), the visualization agent image has a color corresponding to each lymphatic route (e.g., pink for the median forearm route, purple for the radial route, purple for the accessory radial route is blue, the length-side route is red, the vernier-side route is green, etc.). This makes it easier to visually grasp each lymphatic route and facilitate evaluation of the lymphatic system.

The output means D4 outputs the visualization agent image colored by the color setting means. The colored visualization agent image may be output to an output device, output from a communication module to another device, or output to an auxiliary storage device for recording.

[Lymphatic system function evaluation program]
The lymphatic system function evaluation program causes a computer to function as the above-described first acquisition means D1, second acquisition means D2, color setting means D3, and output means D4. The computer operates as a lymphatic system function evaluation device D by loading the lymphatic system function evaluation program into the computer. The lymphatic system function evaluation program is recorded on, for example, a computer-readable recording medium and provided. The recording medium may be a non-transitory recording medium. Examples of recording media include recording media such as flexible discs, CDs and DVDs, recording media such as ROMs, and semiconductor memories.

(Method for evaluating lymphatic system function)
A method for evaluating the lymphatic system function performed by the lymphatic system function evaluation device D will be described. First, the first acquiring means D1 acquires information on the injection site of the visualization agent in the extremity periphery of the subject. Next, the second acquiring means D2 acquires the visualization agent image of the subject injected with the visualization agent. The order of acquisition of information by the first acquisition means D1 and the second acquisition means D2 may be reversed.

Next, the color setting means D3 acquires the information acquired by the first acquisition means, and the information on the lymphatic routes existing in the extremities and the corresponding injection sites on the periphery of the extremities (for example, FIG. 1, FIG. 15 and FIG. 16). , and based on the information of the correspondence shown in FIGS. 2, 31 and 32, or information equivalent thereto (for example, information acquired about further specimens, etc.)), the visualization agent image acquired by the second acquisition means , a different color is set for each lymphatic route that exists in multiple extremities. Next, the output means D4 outputs the visualization agent image colored by the color setting means. For example, a visualizing agent image (for example, a fluorescent image) of the subject's lymphatic system in which each lymphatic route is colored differently is displayed by the output means D4.

Hereinafter, embodiments will be described more specifically based on test examples. All the following tests were conducted under the approval of the Ethics Committee of Okayama University Hospital (K1605-020).

[Test Example 1: Mapping of the lymphatic route of the lower extremities]
<Materials and methods>
Indocyanine green (ICG) lymphangiography was performed on 100 lower extremities (55 males, 45 females) of 53 fresh human cadavers. Prior written informed consent was obtained from all donors.

(ICG lymphangiography test)
25 mg of indocyanine green (Diagnogreen (registered trademark), manufactured by Daiichi Sankyo Co., Ltd.) was dissolved in 10 mL of pure water. Using a syringe needle (30G), 0.05 mL of the ICG solution was injected into the subcutaneous layer of each of the leg injection sites 1-19 shown in FIG. 1 (19 injection sites/1 leg).

Lower extremity injection sites 1 to 19 shown in FIG. 1 were set according to anatomical landmarks on the dorsum-plantar border. Details of each leg injection site are as follows.
Leg injection site 1: Lower medial malleolus Leg injection site 5: head of first metatarsal bone
Leg injection site 6: base of first proximal phalanx
Leg injection site 7: 1st interdigit Lower leg injection site 8: 2nd interdigit Lower leg injection site 9: 3rd interdigit Lower leg injection site 10: 4th interdigit Lower leg injection site 11: 5th proximal phalanx base of fifth proximal phalanx
Lower extremity injection site 12: head of fifth metatarsal bone
Lower extremity injection site 16: Lower lateral malleolus Lower extremity injection site 18: calcaneal tuberosity
Leg injection site 3: midpoint between leg injection site 1 and leg injection site 5 Leg injection site 2: midpoint between leg injection site 1 and leg injection site 3 Leg injection site 4: midpoint between leg injection site 3 and leg injection site 5 Point Lower limb injection site 14: Middle point between lower limb injection site 12 and lower limb injection site 16 Lower limb injection site 13: Middle point between lower limb injection site 12 and lower limb injection site 14 Lower limb injection site 15: Between lower limb injection site 14 and lower limb injection site 16 Middle point lower limb injection site 17: middle point between lower limb injection site 16 and lower limb injection site 18 Lower limb injection site 19: middle point between lower limb injection site 18 and lower limb injection site 1

Immediately after injection of the ICG solution, the injection site was gently massaged by hand. Fluorescent images of ICG were taken with an infrared observation camera system (excitation wavelength 760 nm, fluorescence wavelength 830 nm). Images taken with a slider of an infrared observation camera system were combined with an image composite editor (manufactured by Microsoft Corporation) to obtain a panoramic photograph in which different colors were set for each lymphatic route.

<Results>
(Classification of the lymphatic route of the lower extremities)
FIG. 6A is a photograph (panoramic photograph) showing an example of the results of a lymphangiography examination of the lower extremities. FIG. 6B is a trace diagram of FIG. 6A. The leg was divided at ankle level into four regions (anteromedial, anterolateral, posteromedial, and posterolateral). “Anterior” and “posterior” were defined based on the posterior edge of the lateral malleolus (indicated by “×”) and the anterior edge of the medial malleolus (indicated by “Δ”). The heel side is "rear" and the opposite side is "front" with "x" and "triangle" as boundaries. “Inner” and “outer” are the calcaneal tuberosity (indicated by “○”) and the anterior midpoint between the anterior edge of the medial malleolus and the posterior edge of the lateral malleolus (indicated by “□”). was defined as the criterion. With "○" and "□" as boundaries, the medial malleolus side is "inner" and the lateral malleolus side is "outer".

It has been found that the lymphatic vessels of the lower extremities can be roughly divided into four lymphatic routes, ie, the anteromedial route, the posterolateral route, the anterolateral route, and the posteromedial route, according to the position through which they pass at the level of the ankle joint. In FIG. 6(B), each lymphatic route (anteromedial route, posterolateral route, anterolateral route, or posteromedial route) is distinguished by a different type of hatching.

(Detailed analysis of each lymphatic route)
1. Anteromedial Route FIG. 7A is a photograph showing an example of the result of angiography of the anteromedial route. FIG. 7B is a trace diagram of FIG. 7A. The "□" indicates the anterior midpoint between the anterior edge of the medial malleolus and the posterior edge of the lateral malleolus, and the "◇" indicates the midpoint between the "□" and the tibial tuberosity. The anteromedial root was consistent with the traditionally recognized anteromedial bundle, with an incidence of 100% (100/100).

The anteromedial root starts from most of the dorsum of the foot and repeats many branches and fusions in the dorsum of the foot. The anteromedial root passes anteromedially in a distinct bundle at ankle level (100%: 100/100). Only a minority of cases (4%: 4/100) were cases where the anteromedial root extended to the anterolateral or posteromedial level at the ankle joint level.

The anteromedial root arcs laterally below the lower leg and medially above the upper leg, thus ascending in a sigmoidal fashion. The anteromedial route rarely passed anterolaterally at the midpoint of the crus (15%: 15/100). The anteromedial route moves posterior medially in the middle of the lower leg and passes through the posterior aspect of the knee joint from the medial side, so it goes up in the form of crossing over the great saphenous vein in the middle of the lower leg.

2. Posterolateral Root The posterolateral route is consistent with the traditionally recognized posterolateral bundle, with a prevalence of 92% (92/100).

The posterolateral root originated laterally at the heel and passed posterolaterally as one or two straight lines at ankle level (98.91%: 91/92). Only a minority of cases (4.4%: 4/92) had the posterolateral root extending to areas other than posterolateral at the ankle level.

The posterolateral root ascends to the vicinity of the popliteal fossa and then transitions deep into the thigh. Occasionally, the posterolateral root was also observed ascending the surface of the medial thigh from the popliteal to the groin. A rare instance of the posterolateral root joining with the posteromedial or anterolateral root was observed (7.6%: 4/92).

3. Anterolateral Route FIG. 8A is a photograph showing an example of the result of angiography of the anterolateral route. FIG. 8B is a trace diagram of FIG. 8A. "X" indicates the posterior edge of the lateral malleolus, "□" indicates the anterior midpoint between the anterior and lateral malleolus posterior edges, and "◇" indicates the "□" and the tibial tuberosity. indicates the midpoint between The anterolateral root was located lateral to the anteromedial root (anteromedial bundle) with an incidence of 87% (87/100).

The anterolateral root originates on the lateral side of the dorsum of the foot and has an apparently independent origin (blind end) from the anteromedial root. The anterolateral root rises anterolaterally as one or two straight lines at ankle level, passing through a region distant from the bundle of the anteromedial root.

The anterolateral root is mostly upward on the anterolateral side of the lower leg, but in some cases it may extend significantly to the posterolateral side. The anterolateral root eventually migrates anteromedially, but transitions anteromedially below the midpoint of the crus (11.5%: 10/87), between the midpoint of the crus and the tibial tuberosity. Some migrated anteromedially (49.4%: 43/87) and some migrated anteromedially above the tibial tuberosity (39.1%: 34/87).

The anterolateral root is contiguous with the anteromedial root at the thigh, but does not intersect with the anteromedial root and does not change their relative position. A small number of cases where the anterolateral root joined with the anteromedial root were observed (17.2%: 17/87).

4. Posteromedial Route FIG. 9A is a photograph showing an example of the result of angiography of the posteromedial route. FIG. 9B is a trace diagram of FIG. 9A. "△" indicates the leading edge of the medial malleolus. The posteromedial root was located medial to the anteromedial root (anteromedial bundle) with an incidence of 95% (95/100).

The posteromedial root originates in the middle of the lateral foot and has a separate beginning (blind end) from the anteromedial root. The posteromedial root rises straight on the lower leg or arcs anteriorly. The posteromedial root was mostly burrowed below the anteromedial root (toward the depth of the foot) at the lower leg (69.47%: 66/95). The posteromedial route was the route along the great saphenous vein.

The details of the connection between the posteromedial and anteromedial routes could not be observed due to the intersection of the two routes. However, it was confirmed that the two were connected at least at several points in the lower leg.

FIGS. 10 to 13 are photographs taken after dissection after injecting the dye into the lymphatic vessels of the lower leg. From FIG. 10, it can be seen that the posteromedial route (indicated by the solid arrow) is along the main trunk of the great saphenous vein (indicated by the dashed arrow), and the anteromedial route (indicated by the arrow head) is along the great saphenous vein. It can be seen that it does not accompany the main trunk of the vein (indicated by the dashed arrow). From FIG. 11, it can be seen that the anteromedial route (indicated by the arrow head) accompanies the great saphenous vein branch (indicated by the dashed arrow). From FIG. 12, when the anteromedial route (indicated by the arrow head) is turned over, the posterior medial route (indicated by the solid line arrow) follows along the main trunk of the great saphenous vein (indicated by the broken line arrow). understand even better. From FIG. 13, it can be seen that the posteromedial route (indicated by a solid arrow) exists just above the fascia. FIG. 14 schematically summarizes what can be seen from FIGS. 10 to 13 (FIG. 14(B) is a cross-sectional view of the leg). As shown in Fig. 14, the posteromedial route is the main route along the main trunk of the great saphenous vein, and the anteromedial route, which was conventionally thought to be the main route, is a sub-route along the branch of the great saphenous vein. It turns out that

(Mapping of the origin (blind end) of each lymphatic route in the lower leg)
FIG. 15 is a table mapping the relationship between the lower extremity injection sites 1 to 19 in each cadaver and the corresponding lymphatic route of the lower extremity (anteromedial route, posterolateral route, anterolateral route or posteromedial route). FIG. 16 shows the frequency of imaging possible (number of donors with imaging possible/total number of donors) for each lymphatic route (anteromedial route, posterolateral route, anterolateral route or posteromedial route). It is a graph which shows for every site|part.

As shown in FIGS. 15 and 16, in most cases, the contrast medium was taken up by only one lymphatic route for one lower extremity injection site. was rarely included. On the other hand, there was no uptake of the contrast agent into more than two lymphatic routes from one lower extremity injection site.

As shown in FIGS. 15 and 16, the anteromedial route had a frequency peak (maximum) where imaging was possible at injection sites 7 and 10 of the leg. The posterolateral route had a frequency peak (maximum) where imaging was possible at the leg injection site 16 . The anterolateral route had a frequency peak (maximum) where imaging was possible at lower extremity injection sites 10 and 14 . The posteromedial route had a frequency peak (maximum) in which imaging was possible at lower extremity injection site 1.

<Discussion>
This test revealed that the lymphatic routes of the lower extremities can be roughly divided into four lymphatic routes: an anteromedial route, a posterolateral route, an anterolateral route, and a posteromedial route. These four lymphatic routes existed independently, especially in the lower leg, where there was little confluence between each lymphatic route.

In addition, the contrast agent injection sites that can image these four lymphatic routes are distributed for each lymphatic route on the boundary line between the dorsum and sole of the foot, and the contrast agent is distributed in each lymphatic route for each lower extremity injection site. The probability of incorporation (the frequency at which imaging was possible) was clarified. FIG. 17 is a schematic diagram mapping the area occupied by each lymphatic route (anteromedial route, posterolateral route, anterolateral route, or posteromedial route) in the lower leg based on the results of Test Example 1. FIG.

Since the confluence of each lymphatic route is small in the lower leg, there is a high possibility that the evaluation of the other lymphatic routes will not be sufficient even if only one lymphatic route is imaged from the periphery of the lower extremity as is conventionally performed. Especially in lymphedema, in which lymphatic vessels are degenerated and the lymphatic route is disturbed, it is expected that the lymphatic route that is disturbed is biased because there is a large amount of significant edema on the inside. Therefore, it is considered necessary to evaluate all possible lymphatic routes. Such evaluation is essential for lymphatic venous anastomosis and lymph node transplantation, in which it is important to search for remaining lymphatic vessels/lymph nodes and lymphatic routes. In addition, in all lymphatic angiography methods, it will be necessary in the future to create examination protocols with an awareness of the four independent lymphatic routes.

[Test Example 2: Imaging of lower extremity lymphatic vessels in a patient]
<Method>
The patient was a 72-year-old woman who developed secondary lymphedema (ISL (international society of lymphology) classification stage 2) in the right lower extremity due to pelvic lymphadenectomy and pelvic radiotherapy. There was no edema in the left leg (ISL classification stage 0).

For this patient, lymphangiography of the lower extremities was performed in the same procedure as the ICG lymphangiography examination in Test Example 1. The injection site of the contrast medium was determined with reference to the results obtained in Test Example 1 (in particular, the results shown in FIGS. 1, 15 and 16).

<Results and discussion>
FIG. 18(A) shows the imaging results. FIG. 18(B) is a trace diagram obtained by tracing FIG. 18(A). In FIG. 18B, each lymphatic route of the lower extremities (anteromedial route, posterolateral route, anterolateral route, or posteromedial route) is distinguished by different line types. Anteromedial root: dash-dotted line, posterolateral root: double-dotted line, anterolateral root: solid line, posteromedial root: dashed line.

By injecting the contrast agent from the lower extremity injection site 16 (see FIG. 1), the posterolateral route of the right lower extremity could be imaged halfway down the lower extremity, but it changed into a lymphatic pool (dermal backflow) along the way. The posteromedial root of the right lower extremity could not be imaged from any lower extremity injection site, and when injected into the lower extremity injection site 1 (see FIG. 1), the lymph pool was imaged from the injection site. After injection of contrast at lower extremity injection sites 1 and 16, the anteromedial and anterolateral routes were not enhanced.

Only the anterolateral root was imaged by injecting the contrast agent at lower extremity injection sites 7, 10 and 16 (see FIG. 1) of the right lower extremity. The anteromedial root was missing. The anterolateral route changed into a lymphatic pool in the middle of the lower leg.

In Test Example 1, the appearance rate of the anteromedial root was 100%, and the anterolateral root was imaged from the lower extremity injection site 7 only with a probability of 5%. From this, it can be said that the fact that the anterolateral route was imaged from the leg injection site 7 and that the anteromedial route was not imaged in this patient indicates an abnormal condition.

The patient's left lower extremity was successfully imaged for all lymphatic routes by injecting the contrast agent from lower extremity injection sites 1, 7, 10, 14 and 16. As can be seen from the results shown in FIGS. 15 and 16, by injecting the contrast agent from the lower extremity injection sites 1, 7, 14 and 16, the entire lymphatic route can be imaged.

[Test Example 3: Imaging of Lymphatic Vessels and Lymph Nodes in Lower Limbs]
For each lymphatic route of the lower limbs defined in Test Example 1 (anteromedial route, posterolateral route, anterolateral route and posteromedial route), (i) the first lymph node, (ii) the second and subsequent lymph nodes The nodes and (iii) the running of each lymphatic route were analyzed.

<Method>
Computed tomography (CT) lymphography was performed on 120 lower extremities of fresh human cadavers. Prior written informed consent was obtained from all donors.

(CT lymphography)
Thirty lower extremities per lymphatic route (120 in total for 4 lymphatic routes) were subjected to CT lymphography. First, ICG lymphangiography was performed, and a CT contrast agent was injected directly into the identified lymphatic vessels to obtain CT lymphography images. For imaging studies of all lymphatic routes, ICG solution was injected at lower extremity injection sites 1-19 shown in FIG. 1, and lymphatic vessels were identified based on anatomical features.

Immediately after injection of the ICG solution, the injection site was gently massaged by hand. Fluorescent images of ICG were taken with an infrared observation camera system (excitation wavelength 760 nm, fluorescence wavelength 830 nm). The identified lymphatic vessels were dissected near the ankle joint. The CT contrast medium was prepared by dissolving 5 ml of iodinated poppy oil fatty acid ethyl ester injection (Lipiodol (registered trademark), Guerbet Japan) in 20 ml of diethyl ether. A syringe needle (32G) was used to inject 2 mL of Lipiodol solution directly into the identified and dissected lymphatic vessel.

<Results>
FIG. 19 is a diagram showing the definition of the superficial lymph node group in the groin in this specification (Reference: Foldi's Textbook of Lymphology 3rd Edition for Physicians and Lymphedema Therapists, Editors: Michael Foldi, Ethel Foldi, Published Date: 30th April 2012 , Imprint: Urban & Fischer). As shown in FIG. 19, the superficial lymph node group in the inguinal region is plotted with the great saphenous vein on the vertical axis and the horizontal axis from the saphenous hiatus (confluence with the femoral vein) on the horizontal axis. 3), (2) inferior medial group (IM1-3), (3) superior medial group (SM), (4) superior lateral group (SL) and (5) central group (C). The IL and IM lymph node groups are defined as number 1 (IL1) along the greater saphenous vein, number 3 (IL3) near the horizontal axis, and number 2 (IL2) between them.

(posterior medial route)
FIG. 20 is a three-dimensional constructed CT lymphatic angiographic image showing the running of the lymphatic route when the posteromedial route is angiographically imaged. Lymphatic roots are highlighted in white in the three cross-sectional views of the lower extremities. The posteromedial route ascended along the medial border of the tibia and ran through the layer just above the deep fascia, similar to the actual anatomical findings. The posteromedial root ascended along the posterior border of the sartorius in the thigh. The posteromedial route ran in layers equal to or deeper than the great saphenous vein. The posteromedial route was partly submerged under the deep fascia at the distal thigh and ran near the femoral artery. The run that joins the deep system before reaching the lymph nodes is a finding not found in other lymphatic routes. The posteromedial route generally coincides with the main trunk of the great saphenous vein.

FIG. 21 is a graph plotting the frequency of lymph nodes reached first by the posteromedial route. As shown in FIG. 21, many of the posteromedial routes reached IL1 lymph nodes. A portion of the posteromedial route also reached IL2, IM1-IM3 lymph nodes. In addition, some of the posteromedial routes, although infrequently, merged directly with the deep inguinal lymph node (DI). Joining the DI is a feature not found in other lymphatic routes.

(anteromedial route)
FIG. 22 is a three-dimensionally constructed CT lymphatic angiography image showing the running of the lymphatic route when the anteromedial route is angiographed. Lymphatic roots are highlighted in white in the three cross-sectional views of the lower extremities. The anteromedial route ran across the medial border of the tibia in the lower leg. The anteromedial route runs medial to the sartorius muscle in the thigh. The anteromedial route ran in a layer equal to or shallower than the main trunk of the great saphenous vein.

FIG. 23 is a graph plotting the frequency of lymph nodes reached first by the anteromedial route. As shown in Figure 23, the distribution of lymph nodes reached first by the anteromedial route was similar to that of the posteromedial route, but did not reach the deep inguinal lymph nodes (DI). The anteromedial route also reached IL3, IL2, IM1 and IM2 lymph nodes more frequently than the posteromedial route.

(anterolateral route)
FIG. 24 is a three-dimensional constructed CT lymphatic angiography image showing the running of the lymphatic route when the anterolateral route is angiographed. Lymphatic roots are highlighted in white in the three cross-sectional views of the lower extremities. The anterolateral route passed through the anterior surface of the leg from the outside and transitioned to the medial side of the leg at the proximal leg. The anterolateral route passed anterior to the sartorius muscle in the thigh.

FIG. 25 is a graph plotting the frequency of lymph nodes reached first by the anterolateral route. As shown in FIG. 25, the anterolateral route reached the IL2 lymph nodes the most, followed by the IL1 lymph nodes. A portion of the anterolateral route also reached the SL lymph node group. Reaching the SL lymph node group is a feature not found in other lymphatic routes.

(posterior lateral route)
FIG. 26 is a three-dimensionally constructed CT lymphatic angiographic image showing the running of the lymphatic route when the posterolateral route is angiographically imaged. Lymphatic roots are highlighted in white in the three cross-sectional views of the lower extremities. One or two posterolateral roots were present and ascended the posterior surface of the lower leg. The posterolateral route joined the superficial sub-knee lymph nodes below the knee, then entered the subfascia and mostly ascended along the femoral artery. Part of the posterolateral root branched into the anteromedial or anterolateral group from the lower leg or below the knee, or occasionally mid-thigh.

FIG. 27 is a graph plotting the frequency of lymph nodes reached first by the posterolateral route. FIG. 27 also plots the frequency of lymph nodes reached first by other lymphatic routes (ie, the plots of FIGS. 21, 23 and 25 are also merged). As shown in Figure 27, the posterolateral route mostly reached the superficial sub-kneal lymph nodes (SP). Part of the posterolateral root reached the IL2 or IL1 lymph node by branching out at the lower leg, below the knee, or in the thigh.

Table 1 below shows the frequency of lymph nodes reached first by each lymphatic route in the lower extremities.

FIG. 28 is a graph plotting the frequency of the second and subsequent lymph nodes reached by each lymphatic route in the lower extremity (ie, the lymph nodes reached by each lymphatic route other than the first lymph node reached). As shown in FIG. 28, the posteromedial route leads to SL, IL3, IL2, IM2, IM3, SM, deep inguinal (DI) and C lymph nodes. reached. As shown in Figure 28, the anteromedial route reached the SL, IL3, IL2, IM2, IM3, deep inguinal (DI) and C lymph node groups. As shown in Figure 28, the anterolateral route reached the SL, IL3, IM2, IM3, SM, deep inguinal (DI) and C lymph node groups. As shown in Figure 28, the posterolateral route reached the IL1, IM2, SM lymph node cluster, deep inguinal (DI) and deep below knee (DP) nodes.

As shown in Figure 28, the anteromedial route reached the second and subsequent lymph nodes most frequently. Among them, the anteromedial route most frequently reached the SL lymph node group and could reach any other lymph node. None of the lower extremity lymphatic routes were likely to reach the IL1 and IL2 lymph nodes second or later.

<Discussion>
Comprehensive analysis of the lymphatic routes in the lower extremities revealed that the lymph from the peripheral side of the lower extremities frequently reaches IL1 lymph nodes, IL2 lymph nodes, or superficial sub-knee lymph nodes first. . Lymph from the peripheral side of the lower extremities has a low frequency (possibility) of reaching lymph nodes other than IL1 lymph nodes, IL2 lymph nodes, and superficial below-knee lymph nodes among the superficial lymph nodes in the groin. Lymph nodes other than the IL2 lymph node and the superficial below-knee lymph node are presumed to play a supporting role. In addition, the lymph nodes to which the lymph from the peripheral side of the lower extremity reaches the second and subsequent lymph nodes had countless connections. From the results of Test Example 3, when evaluating the lymph nodes in the lower extremities, IL1 lymph nodes, IL2 lymph nodes, and shallow below-the-knee lymph nodes were targeted for imaging, and the lymphatic system (lymph nodes, lymph vessels) from the periphery of the lower extremities It can be seen that the entire function of can be evaluated.

Conventionally, it was thought that all lymph nodes could be examined by injecting a contrast medium at one site during lymphography examination of the lower extremities. However, the results of Test Example 3 show that the responsible lymph nodes (the first lymph nodes to reach) do not necessarily coincide with each lymphatic route of the lower extremities (anteromedial route, posterolateral route, anterolateral route and posteromedial route). Therefore, it is necessary to comprehensively analyze the lymphatic routes of the lower extremities in order to comprehensively evaluate the lymph nodes. In addition, among the myriad of inguinal lymph nodes, the function can be evaluated separately for the responsible lymph nodes of the lower extremity lymphatic system and the other auxiliary lymph nodes.

[Test Example 4: Mapping of upper extremity lymphatic routes]
<Materials and methods>
Indocyanine green (ICG) lymphangiography was performed on 100 upper extremities of 53 fresh human cadavers. Prior written informed consent was obtained from all donors.

(ICG lymphangiography test)
25 mg of indocyanine green (Diagnogreen (registered trademark), manufactured by Daiichi Sankyo Co., Ltd.) was dissolved in 10 mL of pure water. Using a syringe needle (30G), 0.05 mL of the ICG solution was injected into the subcutaneous layer of each of upper extremity injection sites 1-17 shown in FIG. 2 (17 injection sites/1 upper extremity).

Upper extremity injection sites 1 to 17 shown in FIG. 2 were set according to anatomical landmarks on the dorsum-palm border. Details of each upper extremity injection site are as follows.
Upper extremity injection site 1: distal of radial styloid process
Upper extremity injection site 5: the first head of metacarpi
Upper limb injection site 3: Midpoint between upper limb injection site 1 and upper limb injection site 5 Upper limb injection site 2: Midpoint between upper limb injection site 1 and upper limb injection site 3 Upper limb injection site 4: Midpoint between upper limb injection site 3 and upper limb injection site 5 Point Upper extremity injection site 6: the first interdigital space
Upper extremity injection site 7: the second interdigital space
Upper extremity injection site 8: the third interdigital space
Upper extremity injection site 9: the fourth interdigital space
Upper extremity injection site 10: the fifth head of metacarpi
Upper extremity injection site 14: distal of radial styloid process
Upper limb injection site 12: Midpoint between upper limb injection site 10 and upper limb injection site 14 Upper limb injection site 11: Midpoint between upper limb injection site 10 and upper limb injection site 12 Upper limb injection site 13: Midpoint between upper limb injection site 12 and upper limb injection site 14 Point Upper limb injection site 16: Middle point between upper limb injection site 1 and upper limb injection site 14 (on the palm side)
Upper limb injection site 15: Midpoint between upper limb injection site 14 and upper limb injection site 16 Upper limb injection site 17: Midpoint between upper limb injection site 16 and upper limb injection site 1

Immediately after injection of the ICG solution, the injection site was gently massaged by hand. Fluorescent images of ICG were taken with an infrared observation camera system (excitation wavelength 760 nm, fluorescence wavelength 830 nm). Images taken with a slider of an infrared observation camera system were combined with an image composite editor (manufactured by Microsoft Corporation) to obtain a panoramic photograph in which different colors were set for each lymphatic route.

<Results>
(Classification of upper extremity lymphatic routes)
FIG. 29A is a photograph (panoramic photograph) showing an example of the upper extremity lymphangiography test result. FIG. 29(B) is a trace diagram of FIG. 29(A). Lymphatic routes of the upper extremities were classified into subgroups according to their anatomical course. The lymphatic vessels of the upper extremities run so as to converge in the direction of the axillary lymph nodes, so they are very dense in the upper arm. Therefore, anatomical landmarks were used to classify the running of the lymphatic vessels from the wrist joint to the elbow. As a result, it was possible to divide into five subgroups: Accessory cephalic, Accessory basil, Cephalic, Basil, and Median forearm. (See FIG. 29(B)). Since these generally corresponded to the course of cutaneous veins, they were named accordingly.

Further, as anatomical landmarks, the medial epicondyle of the humerus (indicated by "X" in FIGS. 29 and 30) and the lateral epicondyle of the humerus (indicated by "Δ" in FIGS. 29 and 30). ), radial styloid process (indicated by “□” in FIGS. 29 and 30 ), ulnar styloid process (indicated by “○” in FIGS. 29 and 30 ), and the lymphatic root using the olecranon classified. FIG. 30 is a diagram showing the definition of the upper limb region for explaining the running of the lymphatic route. First, the area between the medial epicondyle of the humerus and the lateral epicondyle of the humerus is divided into four equal parts in the cubital fossa, and zones (Zones) I, II, III and IV are defined in order from the inside, and the olecranon other than zones I to IV is Set as zone V, the running lymphatic route was classified. In addition, on the forearm, on the radial side, the midpoint of the lateral epicondyle of the humerus and the radial styloid process (point R in FIG. 30) is set, and on the ulnar side, the medial epicondyle of the humerus and the midpoint of the ulnar styloid process (point R in FIG. 30) are set. U point) was set and used as an index.

(Detailed analysis of each lymphatic route)
1. The accessory radial route The accessory radial route originates primarily from the dorsum of the hand and runs along the accessory cephalic vein. The incidence of minor radial roots was 94% (94/100). The accessory radial route passes through an average of 2.0 lymphatic vessels at the wrist level, and ascends proximally from the R point while drawing a gentle S-shaped curve to the radial side as a whole, and passes through Zone IV at the cubital fossa. Lymphatic vessels predominated (96%: 86/90). Other cases were observed passing only zone III (3%: 3/94), zone V (1%: 1/94) of the antecubital fossa. Eleven limbs had connections with the vernier root at the forearm (11%: 11/100). In addition, 12 limbs with roots leading to supraclavicular lymph nodes were found (12%: 12/100).

2. Radial Root The radial root originates about the midpoint of the thumb metacarpal bone and runs along the cephalic vein. The incidence of radial roots was 99% (99/100). The radial route passes through an average of 1.8 lymphatic vessels at the wrist level, wraps around the dorsal side of the radial styloid process, reaches the flexor side of the forearm distal to the R point, and passes through the cubital zone III to the upper arm. The leading lymphatics were predominant (96%: 95/99). Another was through the antecubital zone II (4%: 4/99). It runs along the cephalic vein slightly flexor to the accessory radial route. Deep disappearance through the interbiceps muscle lymph node after passing through the antecubital fossa was observed in only 3 cases (3%: 3/95). In the upper arm, near-infrared spectroscopy (NIR) was often indistinguishable due to overlap with the lymphatic vessels of the midline forearm route.

3. The vernier side route The vernier side route mainly originates on the dorsal ulnar side of the hand, wraps around the ulnar styloid process, curves in the ulnar direction of the forearm, and ascends to the flexor side. The incidence of the vernier root was 100% (100/100). The vernilar route was predominantly lymphatic with an average of 2.8 lymphatic vessels at the wrist level, passing through the antecubital zone I to the upper arm (96%: 96/100). The 40 limbs also coexisted with ascending lymphatic vessels through zone V to the upper arm. Many of the lymphatic vessels of the vernical route passed both proximally and distally to the U point of the forearm, and ran widely on the ulnar side of the upper arm.

4. Ulnar Root The ulnar root originates at the volar-dorsal junction of the distal ulna and ascends the forearm along the cutaneous ulnar vein, passing through the cubital zone I to the upper arm. The incidence of the ulnar root was 81% (81/100). The ulnar route was run by one or two lymphatic vessels, which ascended while merging with several lymphatic vessels of the vernicular route on the ulnar side of the forearm.

5. Median Forearm Root The median forearm route originates on the ventral side of the wrist joint, passes through an average of 4.8 lymphatic vessels at the wrist joint level, and ascends the midline of the forearm. The appearance rate of the forearm midline route was 100% (100/100). The forearm midline route leads to the upper arm through the antecubital zone II, gradually converging into one or two lymphatic vessels. On the upper arm, it overlaps with the radial root and ascends.

(Mapping of the origin (blind end) of each lymphatic route in the upper extremity)
FIG. 31 maps the relationship between upper extremity injection sites 1 to 17 in each donated body and the corresponding lymphatic routes of the upper extremity (subradial root, verniular root, radial root, ulnar root, and median forearm root). It is a table. Figure 32 shows the frequency at which imaging was possible for each lymphatic route (subradial route, vernier lumbar route, radial route, ulnar route, and median forearm route) (number of donors with which imaging was possible/total number of ) for each upper extremity injection site.

As shown in Figures 31 and 32, the lymphatic routes corresponding to each upper extremity injection site were nearly identical, indicating that each upper extremity injection site originated from a specific lymphatic route. In addition, although the contrast medium was sometimes taken up by two lymphatic routes from one upper extremity injection site, the contrast medium was never taken up by more than two lymphatic routes. On the dorsal side of the upper limb, the vernilum root had the largest cutaneous lymphatic territory, and on the ventral side of the upper limb, the midline root of the forearm had the largest cutaneous lymphatic territory. Small cutaneous lymphatic territories of the vernier root were also observed in those with a well-developed subradial root. Radial and ulnar root cutaneous lymphatic territories were generally smaller.

<Discussion>
As shown in FIGS. 31 and 32 , the radial route had a frequency peak (maximum) in which imaging was possible at injection site 4 in the upper extremity. The subradial route had a frequency peak (maximum) where imaging was possible at the injection site 7 of the upper extremity. The vernier root had a frequency peak (maximum) at injection site 9 of the upper extremity where imaging was possible. The ulnar root had a frequency peak (maximum) at the upper extremity injection site 14 where imaging was possible. The forearm midline route had a frequency peak (maximum) where imaging was possible at the upper extremity injection site 16 . Also, all five lymphatic routes in the upper extremity can be detected at these five upper extremity injection sites. The anatomical specifications of these five upper extremity injection sites are as follows. The midpoint between the distal radius and the head of the metacarpal of the thumb (upper limb injection site 4), between the second finger (upper limb injection site 7), between the fourth fingers (upper limb injection site 9), ventral side of the distal end of the ulna and dorsal demarcation point (upper extremity injection site 14), wrist ventral midline (upper extremity injection site 16).

FIG. 33 is a schematic diagram mapping the regions occupied by each lymphatic route (the subradial root, the vernier root, the radial root, the ulnar root, and the median forearm root) in the upper limb based on the results of Test Example 4.

In one embodiment, the lymphatic system may be pressurized by lymphatic massage or compression stockings based on the results of lymphatic function evaluation by the lymphatic function evaluation system 1 .

DESCRIPTION OF SYMBOLS 1... Lymphatic system function evaluation system, 3... Imaging device, 3a... Optical filter, 3b... Imaging element, 3c... Imaging element control part, 5... Light irradiation apparatus, 5a... Light source, 5b... Light source control part, 7... Camera unit , D... Lymphatic system function evaluation device, P... Observation object, L1... Excitation light, L2... Observation light, D1... _First acquisition means, D2... _Second acquisition means, D3... Color setting means, D4 Output means D12, D13 Main storage device D14 Input device D15 Output device D16 Communication module D17 Auxiliary storage device.

Claims (4)

a first acquisition means for acquiring information on the injection site of the visualization agent in the peripheral extremities of the subject;
a second acquisition means for acquiring a visualization agent image of a subject injected with a visualization agent;
Based on the information acquired by the first acquisition means and the information on the lymphatic routes present in a plurality of extremities and the corresponding injection sites in the periphery of the extremities, the image of the visualization agent acquired by the second acquisition means has a plurality of presences in the extremities. a color setting means for setting a different color for each lymphatic route;
and an output means for outputting a visualization agent image colored by a color setting means. the computer,
a first acquisition means for acquiring information on the injection site of the visualization agent in the extremities of the subject;
a second acquisition means for acquiring a visualization agent image of the subject injected with the visualization agent;
Based on the information acquired by the first acquisition means and the information on the lymphatic routes present in a plurality of extremities and the corresponding injection sites in the periphery of the extremities, the image of the visualization agent acquired by the second acquisition means has a plurality of presences in the extremities. color setting means for setting a different color for each lymphatic route;
output means for outputting a visualization agent image colored by the color setting means;
Lymphatic system function evaluation program to function as A computer-readable recording medium in which the lymphatic system function evaluation program according to claim 2 is recorded. 4. The recording medium according to claim 3, which is a non-transitory recording medium.

Images